tbuckley/cabot-search huggingface dataset:
Immunotherapy with a standardized Dermatophagoides pteronyssinus extract..
Authors: A. Des Roches, L. Paradis, J. Knani, A. Hejjaoui, H. Dhivert, P. Chanez, J. Bousquet
Journal: Allergy (1996)

Specific immunotherapy (SIT) using a standardized mite extract is effective and safe when administered under optimal conditions. However, the duration of its effectiveness after cessation of treatment remains unknown. Forty asthmatic subjects who had received SIT with a standardized Dermatophagoides pteronyssinus (Der p) extract under the same protocol were studied. All had received SIT for a period of 12–96 months and were not receiving pharmacologic treatment. The FEV 1 was within normal range in all patients. After cessation of treatment, patients were followed for up to 3 years at 6‐month intervals. The patient was considered to have relapsed when symptoms of asthma and/or rhinitis occurred and/or when pulmonary function tests were impaired. Skin tests with increasing concentrations of Der p were carried out before and at the end of SIT. Forty‐five percent of the patients did not relapse. The duration of efficacy of SIT was related to the duration of SIT itself ( P &lt; 0.04). Most patients who did not relapse had a decrease in skin test reactivity at the end of SIT, whereas most patients who relapsed did not show any change ( P &lt; 0.003). The duration of efficacy of SIT after its cessation depends upon the duration of SIT and may be predicted by the effect of SIT on skin tests.
Emergence of resistant Candida auris
Authors: Roxanne Nelson
Journal: The Lancet Microbe (2023)

On March 20, 2023, the US Centers for Disease Control and Prevention (CDC) issued a warning on Candida auris, which is spreading at an alarming rate throughout US health-care facilities and is considered an "urgent antimicrobial resistance threat" by the health agency. Clinical cases of C auris in the USA were first reported in 2016 (n=13 cases) and have increased every year since. Clinical cases increased from 476 in 2019 to 1471 in 2021; colonisation screening volume rose by 80% and screening cases jumped in 2021 by more than 200%.
Reply to the Letter to the Editor ‘Neoadjuvant radiochemotherapy and perioperative chemotherapy does not represent a standard at same priority level for oesophageal adenocarcinomas (in regard to “Oesophageal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up”)’ by Cellini et al.
Authors: R. Obermannová, E.C. Smyth
Journal: Annals of Oncology (2023)
Lessons from COVID-19 for rescalable data collection
Authors: Sangeeta Bhatia, Natsuko Imai, Oliver J Watson, Auss Abbood, Philip Abdelmalik, Thijs Cornelissen, Stéphane Ghozzi, Britta Lassmann, Radhika Nagesh, Manon L Ragonnet-Cronin, Johannes Christof Schnitzler, Moritz UG Kraemer, Simon Cauchemez, Pierre Nouvellet, Anne Cori
Journal: The Lancet Infectious Diseases (2023)
Childhood Acute Lymphoblastic Leukemia: Results of the Randomized Acute Lymphoblastic Leukemia Intercontinental-Berlin-Frankfurt-Münster 2009 Trial
Authors: Myriam Campbell, Csongor Kiss, Martin Zimmermann, Cecilia Riccheri, Jerzy Kowalczyk, Maria S. Felice, Milos Kuzmanovic, Gabor Kovacs, Helen Kosmidis, Alejandro Gonzalez, Ernest Bilic, Luis Castillo, Alexandra Kolenova, Janez Jazbec, Alexander Popa, Dobrin Konstantinov, Janos Kappelmayer, Tomasz Szczepanski, Michael Dworzak, Barbara Buldini, Giuseppe Gaipa, Neda Marinov, Jorge Rossi, Attila Nagy, Imre Gaspar, Jan Stary, Martin Schrappe
Journal: Journal of Clinical Oncology (2023)

The International Berlin-Frankfurt-Münster (BFM) study group conducted a study on pediatric acute lymphoblastic leukemia (ALL). Minimal residual disease (MRD) was assessed using flow cytometry (FCM), and the impact of early intensification and methotrexate (MTX) dose on survival was evaluated.We included 6,187 patients younger than 19 years. MRD by FCM refined the risk group definition previously used in the ALL intercontinental-BFM 2002 study on the basis of age, WBC count, unfavorable genetic aberrations, and treatment response measured morphologically. Patients at intermediate risk (IR) and high risk (HR) were randomly assigned to protocol augmented protocol I phase B (IB) versus IB regimen. MTX doses of 2 versus 5 g/m2 every 2 weeks, four times, were evaluated in precursor B-cell-ALL (pcB-ALL) IR.The 5-year event-free survival (EFS ± SE) and overall survival (OS ± SE) rates were 75.2% ± 0.6% and 82.6% ± 0.5%, respectively. Their values in risk groups were standard risk (n = 624), 90.7% ± 1.4% and 94.7% ± 1.1%; IR (n = 4,111), 77.9% ± 0.7% and 85.7% ± 0.6%; and HR (n = 1,452), 60.8% ± 1.5% and 68.4% ± 1.4%, respectively. MRD by FCM was available in 82.6% of cases. The 5-year EFS rates in patients randomly assigned to protocol IB (n = 1,669) and augmented IB (n = 1,620) were 73.6% ± 1.2% and 72.8% ± 1.2%, respectively (P = .55), while those in patients receiving MTX doses of 2 g/m2 (n = 1,056) and MTX 5 g/m2 (n = 1,027) were 78.8% ± 1.4% and 78.9% ± 1.4%, respectively (P = .84).The MRDs were successfully assessed using FCM. An MTX dose of 2 g/m2 was effective in preventing relapse in non-HR pcB-ALL. Augmented IB showed no advantages over the standard IB.[Media: see text].
US Food and Drug Administration Approval Summary: Nivolumab Plus Platinum-Doublet Chemotherapy for the Neoadjuvant Treatment of Patients With Resectable Non–Small-Cell Lung Cancer
Authors: Oladimeji Akinboro, Nicole Drezner, Anup Amatya, Jin Runyan, Jeanne Fourie-Zirkelbach, Miao Zhao, Youwei Bi, Kwadwo Korsah, Bronwyn Mixter, Shenghui Tang, Erin Larkins, Richard Pazdur, Julia A. Beaver, Harpreet Singh
Journal: Journal of Clinical Oncology (2023)

On March 4, 2022, the US Food and Drug Administration (FDA) approved nivolumab plus platinum-doublet chemotherapy for the neoadjuvant treatment of patients with resectable non-small-cell lung cancer (NSCLC). We discuss the FDA's review of the key data and regulatory considerations supporting this approval.
Impact of Drainage Cannula Size and Blood Flow Rate on the Outcome of Patients Receiving Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: An ELSO Registry Analysis
Authors: Tommaso Mauri, Elena Spinelli, Quazi Ibrahim, Bram Rochwerg, Roberto Lorusso, Joseph E. Tonna, Susanna Price, Graeme MacLaren, Antonio Pesenti, Arthur S. Slutsky, Daniel Brodie
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Impact of Drainage Cannula Size and Blood Flow Rate on the Outcome of Patients Receiving Venovenous ECMO for ARDS: An ELSO Registry Analysis." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Awakening Allies for Breaking Microenvironment Barriers: NIR‐II Guided Orthogonal Activation of Tumor‐Infiltrating Mast Cells for Efficient Nano‐Drug Delivery
Authors: Qingyuan Wang, Haiyan Yang, Yuan Liu, Zhaoxi Zhou, Xu Zhang, Mingyi Sang, Feng Xu, Lebin Song, Tiansong Xia, Yue Zhang, Jifu Wei, Xiaobo Zhang, Qiang Ding
Journal: Advanced Healthcare Materials (2023)

Mast cells (MCs), powerful immune cells that heavily infiltrate cancer cells, play a crucial role in tumor formation. Activated MCs can release histamine and a family of proteases through degranulation effects, concurrently achieving endothelial junction weakening and stromal degradation of the tumor microenvironment, thereby clearing the obstacles for nano-drug infiltration. To achieve precise activation of tumor-infiltrating MCs, orthogonally excited rare earth nanoparticles (ORENP), with two channels, are introduced for the controllable stimulating drugs release wrapped in "photocut tape". The ORENP can emit near-infrared II (NIR-II) for image tracing for tumor localization in Channel 1 (808/NIR-II) and allows energy upconversion to emit ultraviolet (UV) light for releasing drugs for MCs stimulation in Channel 2 (980/UV). Finally, the combined use of chemical and cellular tools enables clinical nano-drugs to achieve a significant increase in tumor infiltration, thereby enhancing the efficacy of nano-chemotherapy.
An interferon gamma response signature links myocardial aging and immunosenescence
Authors: DiyaaElDin Ashour, Sabine Rebs, Panagiota Arampatzi, Antoine-Emmanuel Saliba, Jan Dudek, Richard Schulz, Ulrich Hofmann, Stefan Frantz, Clément Cochain, Katrin Streckfuß-Bömeke, Gustavo Campos Ramos
Journal: Cardiovascular Research (2023)

Aging entails profound immunological transformations that can impact myocardial homeostasis and predispose to heart failure. However, preclinical research in the immune-cardiology field is mostly conducted in young healthy animals, which potentially weakens its translational relevance. Herein, we sought to investigate how the aging T-cell compartment associates with changes in myocardial cell biology in aged mice.We phenotyped the antigen-experienced effector/memory T cells purified from heart-draining lymph nodes of 2-, 6-, 12-, and 18-month-old C57BL/6J mice using single-cell RNA/T cell receptor sequencing. Simultaneously, we profiled all non-cardiomyocyte cell subsets purified from 2- to 18-month-old hearts and integrated our data with publicly available cardiomyocyte single-cell sequencing datasets. Some of these findings were confirmed at the protein level by flow cytometry. With aging, the heart-draining lymph node and myocardial T cells underwent clonal expansion and exhibited an up-regulated pro-inflammatory transcription signature, marked by an increased interferon-γ (IFN-γ) production. In parallel, all major myocardial cell populations showed increased IFN-γ responsive signature with aging. In the aged cardiomyocytes, a stronger IFN-γ response signature was paralleled by the dampening of expression levels of transcripts related to most metabolic pathways, especially oxidative phosphorylation. Likewise, induced pluripotent stem cells-derived cardiomyocytes exposed to chronic, low grade IFN-γ treatment showed a similar inhibition of metabolic activity.By investigating the paired age-related alterations in the T cells found in the heart and its draining lymph nodes, we provide evidence for increased myocardial IFN-γ signaling with age, which is associated with inflammatory and metabolic shifts typically seen in heart failure.
Re: Daniel D. Shapiro, Jose A. Karam, Logan Zemp, et al. Cytoreductive Nephrectomy Following Immune Checkpoint Inhibitor Therapy Is Safe and Facilitates Treatment-free Intervals. Eur Urol Open Sci 2023;50:43–6
Authors: Alireza Ghoreifi, Hooman Djaladat
Journal: European Urology (2023)
Conjugating 4<i>β</i>‐NH‐(5‐Aminoindazole)‐podophyllotoxin and Galectin‐1‐Targeted Aptamer for Synergistic Chemo‐Immunotherapy of Hepatocellular Carcinoma
Authors: Ying Cong, Shu‐Yue Zhang, Paula Yun‐Zhi Tang, Hong‐Mei Li, Xue Liu, Wei Zhao, Ya‐Jie Tang
Journal: Advanced Healthcare Materials (2023)

By conjugating a chemotherapeutic candidate drug 4β-NH-(5-aminoindazole)-podophyllotoxin (βIZP) and an immunosuppressive protein galectin-1 targeted aptamer AP74, a chemo-immunotherapy molecule (AP74-βIZP) is developed against liver cancer. AP74-βIZP can target galectin-1 and enrich the tumor microenvironment to improve the tumor inhibition ratio by 6.3%, higher than that of βIZP in a HepG2 xenograft model. In safety evaluation, βIZP cannot be released from AP74-βIZP in normal tissues with low glutathione level. Therefore, the degrees of organs injury and myelosuppression after the treatment with AP74-βIZP are lower than those with βIZP. After 21 d treatment at a drug dose of 5 mg kg-1 , AP74-βIZP does not cause weight loss in mice, while the weight is significantly reduced by 24% and 14% from oxaliplatin and βIZP, respectively. In immune synergy, AP74-IZP enhances CD4/CD8 cell infiltration to promote the expression of cell factor (i.e., IL-2, TNF-α, and IFN-γ), which further improves the antitumor activity. The tumor inhibition ratio of AP74-βIZP is 70.2%, which is higher than that of AP74 (35.2%) and βIZP (48.8%). Because of the dual effects of chemotherapy and immunotherapy, AP74-βIZP exhibits superior activity and lower toxicity. The approach developed in this work could be applicable to other chemotherapy drugs.
Impact of house dust mite in vitiligo skin: environmental contribution to increased cutaneous immunity and melanocyte detachment
Authors: Hanene Bzioueche, Katia Boniface, Claire Drullion, Sandrine Marchetti, Bérengère Chignon-Sicard, Laura Sormani, Stéphane Rocchi, Julien Seneschal, Thierry Passeron, Meri K Tulic
Journal: British Journal of Dermatology (2023)

Abstract Background Vitiligo is an autoimmune skin disorder characterized by loss of melanocytes. Protease-mediated disruption of junctions between keratinocytes and/or keratinocyte intrinsic dysfunction may directly contribute to melanocyte loss. House dust mite (HDM), an environmental allergen with potent protease activity, contributes to respiratory and gut disease but also to atopic dermatitis and rosacea. Objectives To verify if HDM can contribute to melanocyte detachment in vitiligo and if so, by which mechanism(s). Methods Using primary human keratinocytes, human skin biopsies from healthy donors and patients with vitiligo, and 3D reconstructed human epidermis, we studied the effect of HDM on cutaneous immunity, tight and adherent junction expression and melanocyte detachment. Results HDM increased keratinocyte production of vitiligo-associated cytokines and chemokines and increased expression of toll-like receptor (TLR)-4. This was associated with increased in situ matrix-metalloproteinase (MMP)-9 activity, reduced cutaneous expression of adherent protein E-cadherin, increased soluble E-cadherin in culture supernatant and significantly increased number of suprabasal melanocytes in the skin. This effect was dose-dependent and driven by cysteine protease Der p1 and MMP-9. Selective MMP-9 inhibitor, Ab142180, restored E-cadherin expression and inhibited HDM-induced melanocyte detachment. Keratinocytes from patients with vitiligo were more sensitive to HDM-induced changes than healthy keratinocytes. All results were confirmed in a 3D model of healthy skin and in human skin biopsies. Conclusions Our results highlight that environmental mite may act as an external source of pathogen-associated molecular pattern molecules in vitiligo and topical MMP-9 inhibitors may be useful therapeutic targets. Whether HDM contributes to the onset of flares in vitiligo remains to be tested in carefully controlled trials.
Clusterin Neutralizes the Inflammatory and Cytotoxic Properties of Extracellular Histones in Sepsis
Authors: Jean-François Augusto, Céline Beauvillain, Caroline Poli, Léa Paolini, Isabelle Tournier, Pascale Pignon, Simon Blanchard, Laurence Preisser, Raffaella Soleti, Chloé Delépine, Marine Monnier, Isabelle Douchet, Pierre Asfar, François Beloncle, Olivier Guisset, Renaud Prével, Alain Mercat, Emeline Vinatier, Julien Goret, Jean-François Subra, Dominique Couez, Mark R. Wilson, Patrick Blanco, Pascale Jeannin, Yves Delneste
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Rationale: Extracellular histones, released into the surrounding environment during extensive cell death, promote inflammation and cell death, and these deleterious roles have been well documented in sepsis. Clusterin (CLU) is a ubiquitous extracellular protein that chaperones misfolded proteins and promotes their removal. Objectives: We investigated whether CLU could protect against the deleterious properties of histones. Methods: We assessed CLU and histone expression in patients with sepsis and evaluated the protective role of CLU against histones in in vitro assays and in vivo models of experimental sepsis. Measurements and Main Results: We show that CLU binds to circulating histones and reduces their inflammatory, thrombotic, and cytotoxic properties. We observed that plasma CLU levels decreased in patients with sepsis and that the decrease was greater and more durable in nonsurvivors than in survivors. Accordingly, CLU deficiency was associated with increased mortality in mouse models of sepsis and endotoxemia. Finally, CLU supplementation improved mouse survival in a sepsis model. Conclusions: This study identifies CLU as a central endogenous histone-neutralizing molecule and suggests that, in pathologies with extensive cell death, CLU supplementation may improve disease tolerance and host survival.
Stereochemistry and functions of the new cysteinyl‐resolvin, <scp>4S</scp>,<scp>5R‐RCTR1</scp>, in efferocytosis and erythrophagocytosis of human senescent erythrocytes
Authors: Robert Nshimiyimana, Stephania Libreros, Mélissa Simard, Nan Chiang, Ana R. Rodriguez, Bernd W. Spur, Jesper Z. Haeggström, Charles N. Serhan
Journal: American Journal of Hematology (2023)

Abstract Specialized pro‐resolving lipid mediators play key functions in the resolution of the acute inflammatory response. Herein, we elucidate the stereochemical structure of the new 4S,5R‐RCTR1, a cysteinyl‐resolvin, recently uncovered in human leukocytes incubated with a 4S,5S‐epoxy‐resolvin intermediate, using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and ultra‐violet (UV) spectrophotometry. With this approach, the physical properties of the new mediator prepared by total organic synthesis were matched to enzymatically produced biogenic material. In addition, we confirmed the potent biological actions of 4S,5R‐RCTR1 with human M2‐like macrophage phagocytosis of live bacteria, efferocytosis of apoptotic neutrophils, and erythrophagocytosis of senescent human red blood cells in a concentration‐dependent manner from 0.1 to 10 nM. Taken together, these results establish the complete stereochemistry of 4S,5R‐RCTR1 as 5R‐glutathionyl‐4S,17S‐dihydroxy‐6E,8E,10Z,13Z,15E,19Z‐docosahexaenoic acid and give evidence of its novel bioactivities in human phagocyte responses. Moreover, they confirm and extend the stereoselective functions of the 4S,5R‐RCTR1 with isolated human phagocytes of interest in the resolution of inflammation.
TIGIT Expression Delineates T-cell Populations with Distinct Functional and Prognostic Impact in Pancreatic Cancer
Authors: Max Heiduk, Anna Klimova, Charlotte Reiche, David Digomann, Carolin Beer, Daniela E. Aust, Marius Distler, Jürgen Weitz, Adrian M. Seifert, Lena Seifert
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Immunotherapy has led to a fundamental shift in the treatment of several cancers. However, its efficacy in pancreatic ductal adenocarcinoma (PDAC) is limited. Understanding the expression of inhibitory immune checkpoint receptors (ICR) by intratumoral T cells may help to unravel their involvement in insufficient T-cell–mediated antitumor immunity. Experimental Design: Using multicolor flow cytometry, we analyzed circulating and intratumoral T cells from blood (n = 144) and matched tumor samples (n = 107) of patients with PDAC. We determined the expression of programmed cell death protein 1 (PD-1) and T-cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) by CD8+ T-cells, conventional CD4+ T-cells (Tconv) and regulatory T cells (Treg) and their association with T-cell differentiation, tumor reactivity, and cytokine expression. A comprehensive follow-up was used to determine their prognostic value. Results: Intratumoral T cells were characterized by increased PD-1 and TIGIT expression. Both markers delineated distinct T-cell subpopulations. PD-1+TIGIT− T cells highly expressed proinflammatory cytokines and markers of tumor reactivity (CD39, CD103), whereas TIGIT expression was linked to antiinflammatory and exhausted phenotypes. In addition, the enhanced presence of intratumoral PD-1+TIGIT− Tconv was associated with improved clinical outcomes, while high ICR expression on blood T cells was a significant hazard for overall survival (OS). Conclusions: Our results uncover the association between ICR expression and T-cell functionality. PD-1 and TIGIT characterized intratumoral T cells with highly divergent phenotypes linked to clinical outcomes, further underscoring the relevance of TIGIT for immunotherapeutic approaches in PDAC. The prognostic value of ICR expression in patient blood may be a valuable tool for patient stratification.
Association of Food Deserts and Food Swamps With Obesity-Related Cancer Mortality in the US
Authors: Malcolm Seth Bevel, Meng-Han Tsai, April Parham, Sydney Elizabeth Andrzejak, Samantha Jones, Justin Xavier Moore
Journal: JAMA Oncology (2023)

Obesity-related cancers account for 40% of all cancers in the US. Healthy food consumption is a modifiable factor shown to reduce obesity-related cancer mortality, but residing in areas with less access to grocery stores (food deserts) or higher access to fast food (food swamps) reduces healthy food access and has been understudied.To analyze the association of food deserts and food swamps with obesity-related cancer mortality in the US.This cross-sectional ecologic study used US Department of Agriculture Food Environment Atlas data from 2012, 2014, 2015, 2017, and 2020 and Centers for Disease Control and Prevention mortality data from 2010 to 2020. A total of 3038 US counties or county equivalents with complete information on food environment scores and obesity-related cancer mortality data were included. An age-adjusted, generalized, mixed-effects regression model was performed for the association of food desert and food swamp scores with obesity-related cancer mortality rates. Data were analyzed from September 9, 2022, to September 30, 2022.Food swamp score was calculated as the ratio of fast-food and convenience stores to grocery stores and farmers markets. Higher food swamp and food desert scores (20.0 to ≥58.0) indicated counties with fewer healthy food resources.Obesity-related cancer (based on the International Agency for Research on Cancer evidence between obesity and 13 types of cancer) mortality rates were categorized as high (≥71.8 per 100 000 population) vs low (<71.8 per 100 000 population) per county.A total of 3038 counties or county equivalents with high obesity-related cancer mortality rates had a higher percentage of non-Hispanic Black residents (3.26% [IQR, 0.47%-26.35%] vs 1.77% [IQR, 0.43%-8.48%]), higher percentage of persons older than 65 years (15.71% [IQR, 13.73%-18.00%] vs 15.40% [IQR, 12.82%-18.09%]), higher poverty rates (19.00% [IQR, 14.20%-23.70%] vs 14.40% [IQR, 11.00%-18.50%]), higher adult obesity rates (33.00% [IQR, 32.00%-35.00%] vs 32.10% [IQR, 29.30%-33.20%]), and higher adult diabetes rates (12.50% [IQR, 11.00%-14.20%] vs 10.70% [IQR, 9.30%-12.40%]) compared with counties or county equivalents with low obesity-related cancer mortality. There was a 77% increased odds of having high obesity-related cancer mortality rates among US counties or county equivalents with high food swamp scores (adjusted odds ratio, 1.77; 95% CI, 1.43-2.19). A positive dose-response relationship among 3 levels of food desert and food swamp scores and obesity-related cancer mortality was also observed.The findings of this cross-sectional ecologic study suggest that policy makers, funding agencies, and community stakeholders should implement sustainable approaches to combating obesity and cancer and establishing access to healthier food, such as creating more walkable neighborhoods and community gardens.